3P0G

Structure of a nanobody-stabilized active state of the beta2 adrenoceptor

Summary for 3P0G

• Entry DOI: 10.2210/pdb3p0g/pdb
• Descriptor: Beta-2 adrenergic receptor, Lysozyme, Camelid Antibody Fragment, 8-[(1R)-2-{[1,1-dimethyl-2-(2-methylphenyl)ethyl]amino}-1-hydroxyethyl]-5-hydroxy-2H-1,4-benzoxazin-3(4H)-one (3 entities in total)
• Functional Keywords: beta-2 adrenoceptor, agonist, nanobody, 7tm, gpcr, membrane, signaling protein, hydrolase, membrane protein
• Biological source: Homo sapiens (human, Bacteriophage T4); More
• Cellular location: Cell membrane ; Multi- pass membrane protein : P07550
• Total number of polymer chains: 2
• Total formula weight: 70871.15

Authors

Rasmussen, S.G.F.,Choi, H.-J.,Fung, J.J.,Pardon, E.,Casarosa, P.,Chae, P.S.,DeVree, B.T.,Rosenbaum, D.M.,Thian, F.S.,Kobilka, T.S.,Schnapp, A.,Konetzki, I.,Sunahara, R.K.,Gellman, S.H.,Pautsch, A.,Steyaert, J.,Weis, W.I.,Kobilka, B.K. (deposition date: 2010-09-28, release date: 2011-01-19, Last modification date: 2024-10-30)

Primary citation

Rasmussen, S.G.,Choi, H.J.,Fung, J.J.,Pardon, E.,Casarosa, P.,Chae, P.S.,Devree, B.T.,Rosenbaum, D.M.,Thian, F.S.,Kobilka, T.S.,Schnapp, A.,Konetzki, I.,Sunahara, R.K.,Gellman, S.H.,Pautsch, A.,Steyaert, J.,Weis, W.I.,Kobilka, B.K.
Structure of a nanobody-stabilized active state of the b2 adrenoceptor
Nature, 469:175-180, 2011

PubMed Abstract: G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β(2) adrenergic receptor (β(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11 Å outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation.

PubMed: 21228869
DOI: 10.1038/nature09648

Experimental method

X-RAY DIFFRACTION (3.5 Å)